Catecholamines promote lung edema clearance via -adrenergic-mediated stimulation of active Na⁺ transport across the alveolar epithelium. Because alveolar epithelial type II cell Na⁺-K⁺-ATPase contributes to vectorial Na⁺ flux, the present study was designed to investigate whether Na⁺-K⁺-ATPase undergoes acute changes in its catalytic activity in response to -adrenergic-receptor stimulation. Na⁺-K⁺-ATPase activity increased threefold in cells incubated with 1 µM isoproterenol for 15 min, which also resulted in a fourfold increase in the cellular levels of cAMP. Forskolin (10 µM) also stimulated Na⁺-K⁺-ATPase activity as well as ouabain binding. The increase in Na⁺-K⁺-ATPase activity was abolished when cells were coincubated with a cAMP-dependent protein kinase inhibitor. This stimulation, however, was not due to protein kinase-dependent phosphorylation of the Na⁺-K⁺-ATPase -subunit; rather, it was the result of an increased number of -subunits recruited from the late endosomes into the plasma membrane. The recruitment of -subunits to the plasma membrane was prevented by stabilizing the cortical actin cytoskeleton with phallacidin or by blocking anterograde transport with brefeldin A but was unaffected by coincubation with amiloride. In conclusion, isoproterenol increases Na⁺-K⁺-ATPase activity in alveolar type II epithelial cells by recruiting -subunits into the plasma membrane from an intracellular compartment in an Na⁺-independent manner.